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About Google Book Search Google's mission is to organize the world's information and to make it universally accessible and useful. Google Book Search helps readers discover the world's books while helping authors and publishers reach new audiences. You can search through the full text of this book on the web at jhttp : //books . qooqle . com/ HAROLD C. ERNST. M.D. & sftfrrs^Ze: as 77 THEORIES OF IMMUNITY. The facts in hemolysis and bacteriolysis have led to the investigation of the action of other kinds of cells when introduced into fresh ani- mals. A very large number of different kinds of action of this nature have been studied, and it is demonstrated that it is possible to secure sera of many sorts which have a specific action upon the cells originally used for the production of the cytolytic power. Thus, for example, the study of the results following the injection of living spermatozoa has been the demonstration of the production, in the serum of the animal in which they are injected, of a property that has the power of immobilizing fresh spermatozoa, if not of absolutely dissolving them ; the same thing holds true of other cells. Liver cells in- jected in the same way will produce a serum capable of inducing fatty degeneration of the liver cells of a fresh animal. Of course the pos- sible results that may come from such cytolytic action as this are of the most important nature. The reactions are explained by Ehrlich in the same way as the phenomena of hemolysis and 78 THEORIES OF IMMUNITY. bacteriolysis, and they may be illustrated by formulae similar to those already explained. Thus — cytolysis requires 1. The cell to be acted upon, molecule^H+N+X 2. The immune body (produced by the previous injection of the above) molecule^H-f^T+X 3. The complement . . " =H+h+X And when the H groups have produced the necessary combinations, the L atom group of the complement may exert its lytic action. The production of the cytolytic property may, of course, also be illustrated in the same way as follows : Its production requires 1. The foreign cell to be in- jected .... moleeule=H+]S~+X 2. The tissue cells in which the injection is made, molecule=H+iZ4-]S~+X 3. The complement . molecule=iZH-L+X. The same combinations are supposed to occur in this as in preceding cases : the H atom-groups combine together, so that those needed for proper 79 THEORIES OF IMMUNITY. metabolism of the tissue cells in which the injec- tion is made are used for another purpose — these are reproduced in excess, and cast off into the blood stream, where they exist as substances capable of aiding in the cytolytic action. Both sides, that which supports the w humoral " and that supporting the "cellular" theory, agree in supposing that two bodies are necessary for the production of these reactions, but there are two special points of dispute — first as to whether the complement exists in the cells or out of them; and second, whether it is single and specific for the race of animals in which it occurs, or whether it is multiple and specific only for the reaction in which it appears active. There is no dispute as to the complexity or rather multiplicity of the immune bodies, which are generally acknowledged to be very numerous and capable of action only in special directions — on the particular bacteria or tissue cells, as the case may be. As to the multiplicity of complement, it has been shown that it is possible lo reactivate a serum by the addition of a little fresh serum 80 THEORIES OF IMMUNITY. from an animal of a different species. Such a fact tends to show that complement is the same in all species of animals, although there are other experiments that indicate that this conclusion may not be absolutely warranted. Still another fact that is of importance is the conclusion warranted by the evidence that com- plement and immune body are not produced in the same quantity, which would be expected from the circumstances of the case. An illus- tration is furnished by the possibility of demon- strating that a given quantity of a cytolytic serum may destroy a given quantity of cells. If, how- ever, fresh serum be added, the same quantity of the cytolytic serum will be found capable of dissolving many times the number of cells it could act upon in the first place. The main point of controversy is upon the multiplicity of complement, but not enough evi- dence is yet before us to enable us to form a definite opinion upon the matter. Metchnikoff takes very strong ground in the matter, and de- clares that the complement exists only in the cells of the body, from whence it passes into the 81 THEORIES OF IMMUNITY. blood stream only after some destructive action on the cells, and furthermore that it may take part in the completion of the immunity occurring in many infectious processes as well as in many cell reactions. On the other hand, Ehrlich argues forcibly for the multiplicity of comple- ment, claiming that this substance is multiple and specific for each reaction, as is the case with immune body. Walker (Journal of Hygiene, 1902, Vol. II., p. 85) furnishes the specific evidence of the identical nature of complement coming from dif- ferent animals as follows: he found that the anti-typhoid serum from a horse that has been inactivated by the application of heat — thus de- stroying its complement — may be reactivated by the addition of serum from the rabbit, ox, and the pig (thus adding fresh complement). This may be represented graphically as follows : Anti-typhoid serum contains Complement, molecule =H-fL+X Immune body, molecule=H+jH'+X Other constituents, molecule=P(roteids)+S (alts)+X. 82 THEORIES OF IMMUNITY. If this be heated to 55° C, for one-half hour, the complement is destroyed, and the comple- ment molecule (H+L+X) no longer exists. The serum therefore is incapable of exercising its bacteriolytic property. If now the fresh serum of an ox, rabbit, or pig (containing of course fresh complement (H+L+X)) be added, the same constituents as at first would exist in the anti-typhoid serum, and the bacteriolytic power would be restored. The various facts brought forward show that one of the difficulties that may arise in the treat- ment of diseases of the second order (like ty- phoid fever, cholera, and plague) is in the fact that much more immune body may be formed than there is complement to help make active, and it is possible that this may be the explana- tion of the poor results obtained with antitoxic sera in the diseases just spoken of. Just how this difficulty is to be met has not been shown, but it is true that the apparently simple thing to do, the addition of fresh sera (containing more complement) does not fulfil the requirements, at least so far as experiments have yet gone. 83 THEORIES OF IMMUNITY. The following summary of this part of the subject is exceedingly good (Ritchie, I. c, p. 261) : It is to be observed that the methods by which bacteria are dealt with in the body are similar to those which obtain when many kinds of foreign cells gain an entrance into the latter. The development of artificial immunity against such bacteria depends on the latter being intro- duced either in a form not strong enough to cause death, or, if virulent, not in sufficient numbers to cause death. In either case, the affected animal probably resists infection be- cause it can develop in its body, or already possesses a substance — immune body — which attaches itself to the bacterial protoplasm, and in virtue of this attachment permits another body, the complement, which exists normally in the animal's body, to act on the bacteria, with a fatal result to the latter. In the case of a further infection with bacteria, such as might occur naturally, or as occurs during the process of immunization, then no illness may result, but a fresh formation of immune body may occur. Whether a fresh formation of complement may occur to any extent is a question for further 84 THEORIES OF IMMUNITY. investigation, but in an immune serum the com- plement is always present to a less degree than the immune body. What the nature of these bodies is is unknown, but the complements are less resistant to heat than the immune bodies. Further, the nature of the reaction which takes place between bacteria, immune body, and com- plement is disputed, and lastly, while the multi- plicity of immune body is undoubted it is still open to question whether there is a great number of complements in each animal's body, or whether there is, for each species at least, only one com- plement which is capable of acting in conjunc- tion with a great variety of immune bodies, so as to produce a solvent effect on many different kinds of bacteria. One of the greatest difficulties standing in the way of the supporters of Ehrlich's theories is the existence of the bactericidal property in the blood serum of animals that have not been treated in any way, and at the same time are susceptible to the action of the bacterium that their blood serum will destroy. The well-known fact that the blood serum of the rabbit has a 85 THEORIES OF IMMUNITY. marked bactericidal action upon the anthrax bacillus, whilst the animal itself succumbs very promptly to an infection by these bacilli, is an illustration in point, and is not by any means the only one that can be brought forward. Whether or not this bacteriolytic action is the same as that seen after the condition of immu- nity has been produced has not been shown; if it is the same, its production must be accounted for, and the reactions may be explained in the same way as has been adopted for the illustra- tion of the other parts of Ehrlich's theory; if, however, it is not the same, and its presence seems to show that a bactericidal property of the serum does not of necessity indicate a con- dition of immunity, then the explanation of its appearance and the method by which it acts has not yet been furnished. Somewhat the same position must be taken in regard to the phenomenon of agglutination. The relation of this phenomenon to immunity does not appear to be any more intimate than that of the possession of a bacteriolytic property on the part of the blood serum. Agglutination, 86 THEORIES OF IMMUNITY. moreover, seems to be even less connected with any action of a w specific " nature than the bactericidal property spoken of just now. In this connection it may be of interest to repeat some conclusions reached in an investigation upon this matter some time ago: 1, That the agglutinating property does not lie in and is in no way connected with the flagella of the bac- terisyconcerned. 2, That agglutination is not to be accepted as a specific property connected with a condition of immunity, although this is a difficult idea to give up. 3, That the homolo- gous nature of agglutination cannot be con- sidered a positive characteristic, for how then explain the clumping of typhoid bacilli by diph- theria antitoxine? 4, Finally that no universally applicable theory of agglutination has yet been offered. That of Bordet (Ann. de Hnst. Past., T. XIII., p. 224, 1889) seems to us the most rational yet suggested — that there is an agglutinating agent ("agglutinine ") acting upon an agglutina- ble substance ( w substance agglutinee," the nature of which is not yet determined), and that this reaction occurs not only with bacteria, but with many other elements — globules, casein, and 87 THEORIES OF IMMUNITY. precipitates of various kinds. (Ernst and Robey. Trans. Triennial Congress of Physicians and Surgeons, Vol. V., p. 28, 1900.) If one favors the idea that phagocytosis is the active factor in disposing of bacteria in the oc- currence of immunity from infection, the phe- nomenon of chemiotaxis must be accounted for, both positive and negative. Metchnikoff does this by the supposition that there exis^sub- stances in the immune serum which stimulate the chemiotactic power of the phagocytes toward the invading bacteria. These w stimulines " are supposed by Metchnikoff to exist along with the w cytases," or else to be these bodies themselves, possessing the stimulating property along with the others that have been ascribed to them. Xot enough attention has been paid to the condition of phagocytosis in the phagocyte pro- ducing tissues, after the acute stage has passed away, and on this point there is much to be said. Recently the condition of these tissues has been studied by Roger (Les Maladies Infec- tieuses, Paris, 1902, p. 680 et seq.), and Muir (Journal of Pathology, Yol. VII., p. 161, quoted 88 THEORIES OF IMMUNITY. and summarized by Ritchie, I. c, p. 283 et seq.). "The fact has long been known that in many in- fectious conditions the number of leucocytes in the circulating blood is increased, but these observers were the ones to demonstrate the pronounced germinative activity which occurs in any infection, in the precursors of these cells. With regard to the leucocytic phagocytosis, Muir has shown both experimentally on animals and by observations on man, that in infections where there is a polymorphonuclear leucocytosis, not only is there evidence of an active division of the parent cell in the bone marrow, but so active is this process that the red marrow increases in amount and encroaches on the yellow. In a case of pneumonia, for instance, a few days after the commencement of the disease the red mar- row may have increased so as to occupy a seventh part of the whole medullary cavity of the femur. !Not only, however, does prolifera- tion occur in the site of formation of such an important class of cells as the polymorphonu- clear leucocytes, but Muir has also shown that proliferation occurs during some infections in such fixed cells as those lining the sinuses of 89 THEORIES OF IMMUNITY. lymphatic glands and also in the hyaline cells lying free in the lymph sinuses, which later may be connected with some at least of the large mononucleate hyaline cells of the blood. He further points out that similar hyaline cells — en- dothelial cells, connective cells — proliferate dur- ing infection, as can be shown by mitotic figures being found. It is no doubt the case that in different infections different groups of cells thus proliferate : in typhoid fever, for instance, there is no polymorphonuclear reaction, but here the proliferation of endothelial cells and hyaline cells in lymphatic glands has been observed. Thus while Metchnikoff has insisted with justice on the importance of the local reaction and of the wandering cells of the body in infections, and has noted the occurrence of phagocytosis in other cells (his fixed ameboid cells), he has missed the fact of the great proliferative changes in various parts of the body which may be de- scribed as the reaction of the body generally against infection. It must be insisted upon that there are not only local chemiotactic effects, but in the case of the wandering cells there is the general chemiotactic effect which draws the 90 THEORIES OF IMMUNITY. polymorphonuclear leucocytes from the marrow, and in all cases of severe infection there is the further stimulative effect which leads cells in various parts to divide. Either this stimulation is part of a reparative process, or it is to be looked on as the result of injury due, say, to cir- culating poisons. The fact that in relation to one aspect of the process, namely, the polymor- phonucleate reaction, the effect is often to in- crease at a given point the available number of cells capable of playing the part of phagocytes leads one to think that all these tissue changes may be. of the nature of an exaggeration of nor- mal functions, the general effect of which ex- aggeration is to have a beneficial effect. It is to be noted as a very important point in this pro- cess that most of the distant effects must be due, even in the case of bacteria which in vitro do not produce soluble poisons, to the circulation of soluble toxines, unless — which is possible — we consider bacteria capable of exerting purely physical influences. Connected with these is the other very important fact that embryonic activity may be dissociated from any actual phagocytosis on the part of the proliferating 91 THEORIES OF IMMUNITY. cells, and this taken along with such facts as the proliferation in certain infections of the non- phagocytic eosinophilic leucocytes raises anew the question of the possible secretion of chemical substances into the serum which may be con- cerned in the complicated process by which bac- teria are destroyed in the animal body. It may also be noted here that Muir has observed an increase in the size and distinctness of the gran- ules in the young polymorphs which occur in the marrow during a severe infection. This might indicate the preparation of material to be secreted. So that from what has just been said it is thus possible that on the fixed cells of the body and the fixed precursors of the wandering cells are impressed qualities which perpetuate immunity in an animal which has survived an infection." (Ritchie, I. c, p. 283.) Such a conclusion as that just drawn is at least in part in direct accord with Metchnikoff's assertion that there is an inheritance of a ten- dency towards phagocytosis by the descendants of cells upon which the property has been impressed. 92 THEORIES OF IMMUNITY. In concluding his review, Ritchie brings for- ward (p. 452, et seq.) the further considerations that follow, and says in regard to them, in substance, that in the first place it is difficult to see how, granted that two substances are necessary for the production of immunity (the immune body and the complement), these sub- stances are to meet the bacterial cell in the first instance except in the body cell. Unless all immune bodies are existent in the serum as w go- betweens " (amboceptors) — substances of an identical nature except that they are utilized for the normal metabolism of the cell until needed for the reactions occurring in immunity — how can the bacterium when it first enters the body come in contact with the immune body for which it has an affinity? The receptor is in the cell (as represented in the formula used to illustrate the reaction) and the bacterial cell receptor must also get into the tissue cell — except it be sup- posed that they exist under normal conditions in the blood stream. It is undoubtedly possible that the immune body may exist in the blood stream as the result of normal metabolism, but this is the only supposition which would explain 93 THEORIES OF IMMUNITY. how it gets there; if it does not so exist, then the bacterium must be conceded to enter the tissue cell at the first in order to start the exci- tation resulting in the production of the immune bodies; if this be the explanation, then Metch- nikoff 's contention that phagocytosis — at least cellular action — takes place in the very first instance must be adopted. In the second place the query arises as to why, if the bacteria must meet both complement and immune body in the cell, why is the latter produced so much in excess and not the former? On the basis of the supposition that the comple- ment exists normally, and that the immune body is the result of an excess of cell activity set in motion by the taking up of the hapto- phorous atom-groups needed in the ordinary metabolism by the bacterial atom-groups of the same nature, this is easily understood, because this new vital activity goes on in excess and may be supposed to result in the production of a great excess of the atom-groups representing the immune body. It is most probably the case that the reactions 94 THEORIES OF IMMUNITY. occurring in the production of immunity are closely related to those that go on under the ordinary conditions of tissue metabolism, and the only way in which this can be settled is by the determination, in the first place, of what the nor- mal functions of the cells are ; and in the second, whether substances similar to the anti- bodies exist under normal conditions in the body. Inquiry in the first direction has as yet left much obscurity to be cleared away, and the exact functions of the leucocytes, or of the cells from which they are derived, are not clearly understood. As to the second point, so many investigations have seemed to show the facts that it can hardly be doubted that substances closely allied to if not identical with both complement and immune body do exist in the sera of normal animals — it is, however, disputed as to whether they exist free in the normal blood stream. If they do so exist they must have some normal function, for it is not to be supposed that they exist for the sole purpose of taking part in the specific reactions of immunity when such necessity may arise. They must take some part in normal tissue metabolism ; and in attempt- 95 THEORIES OF IMMUNITY. ing to determine what these functions were Bordet first called attention to the occurrence of the so-called w precipitines." (Ann. de l'Inst. Past., 1899, T. XIII., p. 225.) He found that in treating rabbits with chicken's blood, a hemolytic serum could be obtained; but also, that when this hemolytic rabbit's serum was added to chicken's blood a precipitate made its appear- ance. Many such precipitates have been obtained with many kinds of blood, and also with many kinds of bacteria as well. Their nature is not well understood, but the reactions seem to be specific and most exact, and these reactions are of great medico-legal value in the determination of the presence of human blood in suspected stains. The general reaction may be shown by the same formulae as were used for the purpose of illustrating the forms of immunity as follows : The production of the precipitate requires : 1. The blood globule, molecule=H+N+X 2. The immune body, " = H+ JT+X 3. The complement, " = H+Y+X 96 THEORIES OF IMMUNITY. The complement and the immune body are bound to the blood corpuscle molecule, and the P atom-group acts in such a way as to produce the precipitate. The production of the precipitine power re- quires : 1. Blood serum, molecule=H+N+X 2. The body cell, molecule=H+£r-fN+X 3. The complement, molecule=jET+P+X The complement and the blood serum mole- cule are bound to the tissue cell by the H atom- groups; these latter in the tissue cell molecule are reproduced in excess and are thrown off after this reproduction occurs and exist free as H+jET+X=the immune body, ready for the pro- duction of the precipitine reaction when the need arises. Any specific reaction — as that resulting from the addition of rabbit's blood to the goat — may be represented by the addition of the sub-letters desired. The belief that the affinities existing in the body cells are very numerous is forced upon the 97 THEORIES OF IMMUNITY. supporters of Ehrlich's explanation of the reac- tions that occur, and this is especially emphasized by the formulae presented in illustration. It is to be supposed that these affinities are con- cerned under normal circumstances in helping on the normal food metabolism of the tissue cells, and possibly other reactions. Ehrlich has given the name of f *haptine" to the whole group, and that the number is great may be seen by those already known — lysins, aggluti- nines, precipitines, complements, ferments, anti- complements, ferments, etc. The production of an anti-complement, for ex- ample, may be represented as follows : it may be obtained by injecting serum containing com- plement from one animal (e.g., a guinea-pig) into another (e.g., rabbit) : The injected serum, molecule=H+L+X The receiving blood cell, molecule=H+(H+H +H+H+H)+N+X The two are bound together, the special H group is reproduced in excess, is thrown off, and exists as H+X=the anti-complement. 98 THEORIES OF IMMUNITY. The action of this anti-complement may be very simply represented : The anti-complement molecule=H+X The complement molecule =H+L+X But the two are bound together, and therefore the L atom-group cannot be bound to anything else, and therefore cannot do any harm or assist in the ordinary action of the complement with the immune body. 99 THEORIES OF IMMUNITY. IV. SUMMARY. A study of the present position of the two main theories explanatory of immunity shows that they are not so far apart as is generally supposed. Both sides agree that the phenomena seen in active immunity require two substances (immune body or substance sensibilisatrice, and comple- ment or alexine). One side, however, insists that these sub- stances remain in the cells (phagocytes). The other maintains that they exist in the blood stream (although, as has been seen, cell activity is necessary for the production of the immune body, at least). This latter fact of itself pro- hibits the belief in a purely humoral explanation of immunity. Both sides agree that w immune body " (sub- stance sensibilisatrice) varies, is multiple and 100 THEORIES OF IMMUNITY. specific for each reaction in which it occurs; one for typhoid, one for diphtheria, and so on. They do not yet agree, however, that w com- plement " (alexine) is multiple. One side main- tains that it is the same for all reactions, the other that it differs and is specific for each. The point that has been insisted upon by Metchnikoff from the beginning is maintained: that in all reactions the cell activity must inter- vene at some stage of its production. 101 THEORIES OF IMMUNITY. SUMMARY OF METHOD OF ILLUSTRATING REACTION. Let H represent the haptophorous atom-group in the molecule. T represent the toxophorous atom-group in the molecule. N" represent the nutrient atom-group in the molecule. L represent the lysin atom-group in the molecule. X represent the remainder of the molecule. It is not necessary to separate the U atom- group; it is done, however, to make clearer the fact that there is some vital action going on. Then to represent the interaction of toxine and antitoxine the following may be used: Toxine molecule contains . . . H+T+X Antitoxine molecule contains . . H+X 102 THEORIES OF IMMUNITY. The two H groups are bound together, thus: /II+T+X \H+X therefore the T group in the toxine cannot be bound to anything else, and the substance exists as a harmless material in the blood stream. The production of the antitoxine by the injec- tion of the toxine maybe represented as follows: Tissue cell molecule contains . . H+N+X Toxine cell molecule contains . . H+T+X The H groups bind the two together; but the H group of the tissue cell molecule is nec- essary for the metabolism of the cell ; it must be reproduced if the cell is to live; being so repro- duced the reproduction occurs in excess, and then the H groups are thrown off and exist free in the blood stream as H+X, which is the antitoxine. Bordet's work on Hemolysis, and Ehrlich's later work, showed that two substances were necessary for other reactions, and necessitated the supposition of the existence of two hapto- phorous atom-groups. In accordance with this 103 THEORIES OF IMMUNITY. idea the reaction in hemolysis may be shown thus: It requires the cell to be destroyed, the im- mune body, and the complement. The cell molecule contains .... H+N+X The immune body molecule con- tains H+/7+-X The complement molecule con- tains JT+L+X The complement is bound to the immune body by one H group, the two to the blood cell by the other H group in the immune body, and then the L group in the complement may act. In cases where two H groups occur, the different affinities are indicated by capital and italics. The production of the immune body requires blood cells injected, the cells of the body in which the injection is made, and the complement. The reaction is shown thus: The blood cell molecule con- tains H+N+X The body cell molecule con- tains H+J7+N+X 104 THEORIES OF IMMUNITY. The complement molecule con- tains JT+L+X The two H groups in the tissue cell molecule are used up, but must be reproduced; being re- produced, this occurs in excess; they are thrown off and exist free in the blood stream as H+ZZ+X, which is the immune body. So with Bacteriolysis: the formulae are the same, except in this instance the cell to be acted upon is the bacterial cell, and not the blood cell: The bacterial cell, molecule con- tains H+T+X The immune body, molecule con- tains H+Z7+X The complement, molecule con- tains iZ4-L+X As before the H groups in the complement and the immune body combine, and then these two are joined to the bacterial cell molecule by the remaining H groups, and thus the L group in the complement may exert its destructive action upon the bacterium. 105 THEORIES OF IMMUNITY. The production of the bacteriolytic power re- quires the bacterial cell to be injected, the tissue cell from which the immune body is to be produced, and the complement existing in the fresh blood stream. The reaction is as follows : The bacterial cell molecule con- tains H+T+X The tissue cell molecule contains H+ ZiT+N-f-X The complement molecule con- tains .ZaT+L+X The H atom-groups in the tissue cell molecule being taken up, are reproduced, cast off, and exist free in the blood stream as H+jET+X, the immune body. Cytolytic action may also be shown: The cell molecule to be acted upon contains H+N+X The immune body molecule contains H+JET+X The complement molecule contains . JZ+L+X The H groups are joined together, and the L group of the complement may then act. The production of the cytolytic property is secured thus: 106 THEORIES OF IMMUNITY. The foreign cell molecule in- jected contains . . . H+N+X The tissue cell molecule, in the body in which injection is made, contains . . H+jER-N+X The complement molecule con- tains 1ZH-L+X The H groups in the tissue cells are repro- duced in excess, and exist free as H+jBT+X the immune body active in cytolysis. Precipitine reactions may also be shown : The blood globulin molecule contains H-KNT+X The immune body molecule contains H+jBT+X The complement molecule contains . liT+P+X The H groups being bound together, the L atom-group may act, in this instance producing the precipitate, and therefore it may be more clearly represented as P. The production of the precipitine power occurs as in all the others : Blood injected, the molecule con- tains H+N+X 107 THEORIES OF IMMUNITY. The cell (of the body in which the injection is made) the molecule contains H+^+N+X The complement (molecule con- tains) H+F+X The H groups are reproduced in excess as before, and exist free as H+//+X, the immune body necessary for this reaction. Anti-complement reaction is shown : The complement molecule contains . H+L-KX The anti-complement molecule con- tains H+L The two H groups combine, and the comple- ment is rendered harmless by this combination. The production of the anti-complement is shown thus : The injected serum (containing complement) molecule contains H+N+X The receiving blood molecule contains H+(H +H+H+ H+etc.) +N+X. The two H atom-groups combine, the one in 108 THEORIES OF IMMUNITY. the receiving blood is renewed in excess, is thrown off and exists free as H+X, the anti-complement. It is of course to be understood that the let- ters and formulae given above are representative of the general reaction only, in each case. If it be desired to express a specific reaction — as for instance that of the diphtheria antitoxine — it may be done by placing a sub-letter w d " in each place where its need is felt; for example, H D +X, with the sub-letter at II, represents the special reaction used for illustration in diphtheria; any other reaction may be shown in its specific nature by the same means. The molecule must also be supposed to con- tain, in the letter X, all the other atom-groups not needed for the expression of the special reac- tion under consideration. [Notb. — The use of H and H to indicate the binding of the com- plement and the immune body, and of these two to the cell, was sug- gested almost simultaneously by Prof. Neisser, of Frankfurt, and Dr. Grunbaum, of Liverpool, and had been adopted when their letters came.] 109 THEORIES OF IMMUNITY. VI. GLOSSARY. Active immunity : more or less permanent im- munity, the result of the use of gradually increasing doses of the toxines of a bac- terium. Addiment : another term, used by Ehrlich, for complement. Agglutinines : substances found in the blood (and possibly elsewhere) during and after the progress of an infectious disease, capable of clumping the bacteria producing the infec- tions; non-specific; not dependent upon a condition of immunity. Alexines : substances existing in the serum of both immune and non-immune animals (per- haps of different nature in each) possessing bactericidal properties. May be free in the blood stream, or always 1 , except by accident, in the leucocytes. no THEORIES OF IMMUNITY. Alexines : (Bordet) bodies recognized by Bordet as existing in the cells and possessed of bac- tericidal properties; because of the fact that they may be destroyed by heat (55° C), and thus resembling Buchner's bodies of the same name, Bordet called them alexines; probably the same as the complement of others. Amboceptors: receptors of the third group, capable of becoming normal factors in meta- bolism ; (Zwischen-korper, go-betweens ;) immune bodies. Anti-complement: a substance produced in the blood of an animal, injected with serum containing only complement (no immune body) ; it acts against the complement, and prevents the latter from acting with the immune body. Anti-immune body: a substance that may be supposed to exist in the blood of an animal treated with immune serum in which only "immune body" exists — the complement having been destroyed. Anti-infectious: term used by Metchnikoff to in THEORIES OF IMMUNITY. denote the condition of resistance to further injections of the infectious agent. Anti-sera : the sera of animals which have been treated in such a way as to produce in them substances antagonistic to various bodies ; e.g., bacteria, toxines, blood-corpuscles, etc. Most commonly used to denote antitoxic sera. Antitoxic immunity : passive immunity. Antitoxine unit: the amount of immune serum necessary to exactly neutralize one hundred minimal lethal doses of toxine, after being mixed one-half hour. Atom-groups: atoms of the molecule supposed to have special affinities ; become recep- tors. Autolysin : a substance in serum capable of dis- solving the animal's own blood ; existence not demonstrated. Bacteriolysis: the breaking up of bacteria by substances present in certain sera ; differ- ing from proteolysis in that the bacteria may not be dead. 112 THEORIES OF IMMUNITY. Chemiotaxis : the property of certain cells of being attracted towards (positive) or re- pelled from (negative) foreign bodies, such as bacteria, or irritant substances. Complement: first conceived by Ehrlich, in an extension of his antitoxine theory, to ac- count for the facts in immunity against infection. Exists normally in serum and is destroyed after an exposure of one-half hour to 55° C. Must act with the immune body to produce hemolysis, bacteriolysis, etc. Contains two atom-groups of affini- ties, one binding it to the immune body, the other exerting the active lysin action (hemolysis, bacteriolysis, etc.) ; this cor- responds to the toxophorous atom-group in the toxines. Perhaps the same as alexines of Bordet. Cytase : Metchnikoff 's term for the substance existing in the phagocytes, which acting through, or with the immune body, destroys the bacteria. It is single of its kind ; cor- responds to the complement of Ehrlich, except that the latter is said to be of many kinds and to exist in the blood stream. 113 THEORIES OF IMMUNITY, Enzymes: non-organized ferments, capable of causing splitting or decomposition of other substances without entering into combina- tion with them or their products. Fermentation : the process in which a body may originate changes in other bodies, whilst remaining unchanged itself. Fresh animal : fresh sera, etc. ; not treated in any way to produce any form of immunity. Globulins : albuminous bodies, insoluble in water, but soluble in dilute neutral salt solutions ; possibly the active principle of the antitoxines. Go-betweens : see Zwischen-korper. Haptines : Ehrlich's name for all the groups of receptors. Haptophorous (binding) : applied to groups of affinities in body and bacterial cells, as well as in toxines and immune bodies in general ; satisfied by corresponding affinities in other bodies; receptors. 114 THEORIES OF IMMUNITY. Hemolysis : breaking up of red corpuscles, see lysins. Three factors are necessary for the production of the phenomenon : 1, red-blood corpuscles to be acted upon ; 2, a body oc- curring in the serum of immune animals and resisting heat up to 65° C, i.e., the im- mune body ; 3, a body not resisting heat above 55° C, and occurring in the blood of a fresh animal, i.e., the complement. "Horror autotoxicus^ : Ehrlich's expression for the fact that the tissues seldom, if ever, pro- duce antibodies to receptors already exist- ing in them. Immune body : exists in the serum of an immu- nized animal; resists one-half hour at 75° C. ; has two haptophorous atom-groups, one satisfied by a receptor in the cell binding them together, the other satisfied by a receptor in the complement binding these two together. Immunity: Natural, exists in many animals to many infectious diseases. Acquired, may be the result of an attack of a disease, or the result 115 THEORIES OF IMMUNITY. of artificial procedures. If the latter, it may be Active: the result of the use of toxines, or Passive: the result of the use of antitoxines. Immunity unit : see antitoxine unit. Inactivated: used especially to denote the de- struction of the complement in an immune serum by exposure to heat (55° C), thus making the immune body inactive. Infection : often applied to the action of the bac- teria, as distinct from that of their toxines. Intermediary body : see Immune body. Intoxication : applied to the results of the action of bacterial poisons as distinguished ' from that of the bacteria themselves. Isolysin: a substance produced artificially in serum, capable of destroying the blood cor- puscles of animals of the same species. Isopathic immunity : term suggested by Behring to indicate the immunity of the individual cell (the condition he thinks probably ob- tains in active immunity) ; immunity secured by the use of toxines. 116 THEORIES OF IMMUNITY. Leucopenia: absence or disappearance from a part of all phagocytes or wandering cells ; occurs temporarily in intraperitoneal injec- tions. (Metchnikoff.) Lysins : see Spermatolysin. Macrocytase : cy tase derived from the macropha- gocytes, and active in the destruction of blood corpuscles (hemolysis) . (Metchni- koff.) Macrophagocytes : large mononuclear leucocytes of the blood and of the endothelium, and also, according to Metchnikoff, from the large cells lining the sinuses of the lymph glands and the sinuses of the spleen. Microcytase : cytase derived from the micropha- gocytes, and concerned in the destruction of bacteria. (Metchnikoff. ) Microphagocytes : polymorphonuclear leucocytes. Minimal lethal dose (M.L.D.): the amount of any toxine necessary to kill a two hundred and fifty gram guinea-pig in four days, after subcutaneous injection. Passive immunity : more or less temporary im- munity, the result of the use of the serum of 117 THEORIES OF IMMUNITY. an animal already subjected to active immu- nity (antitoxine immunity). Peritoneum : the French conception is w of a great opened-out gland (un ganglion lymphatic etale), whose cells have proliferative and protective powers, and whose removal renders an animal more susceptible to bac- terial infection than usual." (Ritchie.) Pfeiffers reaction (or Phenomenon) : the disinte- gration of bacteria resulting when these, together with immune serum, are injected into the peritoneal cavity of a fresh animal. The starting point of all the recent work on bacteriolysis, hemolysis, etc. Phagocytosis : the property possessed by certain fixed and free ameboid cells of englobing and digesting bacteria and other bodies. Supposed by Metchnikoff to be derived from the cells of the mesoderm. Phagolysis : partial or complete destruction of phagocytes, used especially in connection with intraperitoneal injections in Pfeiffer's phenomenon. (Metchnikoff.) Precipitines : substances found in the blood of an animal, after injection with blood of an- us THEORIES OF IMMUNITY. other species of animal, capable of producing a precipitate in the blood of the same species of animal from which the injections were made. The precipitate found is soluble (in some cases at least) in two per cent solu- tion of sodium chloride, and is therefore not a coagulation. Proteolysis : the breaking up of proteid bodies as seen in ordinary digestion in connection with the intestinal glands; takes place in dead material. Reactivated : used to denote the supplying of fresh complement to an immune serum, pre- viously made inactive by heat (55° C), thus making the immune body active. (See Inac- tivated.) Receptors: chemical affinities conceived by Ehrlich as existing in the blood corpuscles, other tissue cells, etc.; satisfied by corre- sponding affinities in other substances (im- mune bodies, toxines, etc.). Receptors of the first order : affinities in the cell concerned with fixing relatively simple ma- 119 THEORIES OF IMMUNITY. terials, i.e., toxines, ferments and other cell- ular secretions. Receptors of the second order: affinities in the cell, fixing the molecule by one arm and breaking it up with another of a ferment- like capacity; more complicated and for ab- sorbing molecules of large size. Receptors of the third order : affinities fixed in the cell, and also containing two hapto- phorous atom-groups, one fixing the food particles, the other fixing the ferment-like body (complement), whose action is neces- sary for breaking up the particle fixed; the most important of the three groups. Sensitizing substance {substance sensibilisatrice) : see Immune body; it is the same, except that it is supposed to exist in the cell rather than in the blood stream. Side-chains: see Receptors. The term w side- chains " should be used only of a molecule whose composition is known. Spermatolysin {and other lysins) : refer to ex- periments made with certain cells, after in- jecting which sera can be obtained contain- 120 THEORIES OF IMMUNITY. ing substances capable of destroying these cells. Stimulines : Metchnikoff 's term to denote bodies existing in immune sera, which stimulate the phagocytes to move in a special direc- tion, englobe, and digest invading bac- teria. Tetanus sine tetano : used by Donitz to describe the condition of a rabbit dying after injec- tions of tetanus toxine and antitoxine not quite balanced; death from marasmus, but no tetanus. Tetano-lysin : a substance existing in some bouillon cultures of the tetanus bacillus, capable of destroying red-blood corpuscles of certain animals; destroyed by heat at 50° C. (Madsen.) Tetano-spasmin : what is usually considered the tetanus toxine; with no hemolytic power; very slightly affected by twenty minutes at 50° C. (Madsen.) Toxine immunity : active immunity. Toxophorous (poison carrier} : the group of chemical affinities in the toxine molecule 121 THEORIES OF IMMUNITY. (and in the bacterial cell molecule in certain cases) that exerts the poisonous action on the cell, or is neutralized by the antitoxine. Toxines : the powerful poisonous substances elaborated during the growth of many bac- teria; the soluble toxines are those remain- ing in the filtrate of fluid cultures of some bacteria. Toxoids: the less poisonous substances remain- ing in a filtered culture when this has been kept for some time, and after the soluble toxines have disappeared. Toxones : supposed by Ehrlich to exist along with toxines and toxoids and possessing hapto- phorous atom-groups having a less strong affinity for similar groups in antitoxine or cell than toxine; capable, however, of combining with antitoxine, and of pro- ducing veiy slow poisonous results (e.g., diphtheria paralyses). Vital nucleus: Ehrlich's term for his conception of a centre of vital activity existing in the protoplasm of the cell, with which are asso- ciated the special cell capacities. 122 THEORIES OF IMMUNITY. Zwischen-lcdrper : bodies in normal sera capable of linking the hemolysin (or other lysine) to the cell; corresponding to the immune bodies in immune sera. [Note. — This glossary contains terms found in general reading, as well as those in the text.] 123